Methods, Devices, Kits and Systems for Defunctionalizing the Cystic Duct

ABSTRACT

The application discloses devices, systems, kits and methods for treating biliary disease. Devices comprise, for example, a component configurable for deployment between within a cystic duct of a patient which has a proximal end and a distal end. In some embodiments, a lumen may also extend therethrough.

CROSS-REFERENCE

This application claims the benefit of U.S. Provisional Application No.60/991,682, filed Nov. 30, 2007, and Application No. 61/033,368 filedMar. 3, 2008, which application is incorporated herein by reference.

This application has related subject matter to U.S. Utility patentapplication Ser. No. 12/______, filed Nov. ______, 2008, entitled“Methods, Devices, Kits and Systems for Defunctionalizing theGallbladder” by Jacques Van Dam, J. Craig Milroy, and R. Matthew Ohline(identified as Attorney Docket No. 36233-701.202) and U.S. Utilitypatent application Ser. No. 12/______, filed Nov. ______, 2008,entitled, “Biliary Shunts, Delivery Systems, Methods of Using the Same,and Kits Therefor” by Jacques Van Dam, J. Craig Milroy, and R. MatthewOhline (identified as Attorney Docket No. 36233-701.201), whichapplications are incorporated herein by reference.

FIELD OF THE INVENTION

The invention described in this patent application addresses challengesconfronted in the treatment of biliary disease. Biliary disease includesconditions affecting the gallbladder, cystic duct, and common bile duct.

BACKGROUND OF THE INVENTION Biliary System Function and Anatomy

Bile is a greenish-brown digestive fluid produced by the liver 10illustrated in FIG. 1, and is vital for the digestion of fatty foods.Bile is secreted by liver cells and collected by a network of ducts thatconverge at the common hepatic duct 12. While a small quantity of biledrains directly into the lumen of the duodenum 30 (the section of smallintestine immediately downstream of the stomach), most travels throughthe common hepatic duct 12 and accumulates in the lumen of thegallbladder 14. Healthy gallbladders are pear-shaped sacs with amuscular wall that, on average, measure 10 cm in length and can storeapproximately 50 ml of fluid within its lumen. When fatty foods areingested, the hormone cholecystokinin is released, which causes thegallbladder 14 to contract. Contraction of the gallbladder 14 forcesbile to flow from the gallbladder 14, through the cystic duct 16, intothe common bile duct 18, out the papilla 28, and finally into theduodenum 30 of the small intestine. Here, it mixes and reacts with thefood that exits the stomach. The Sphincter of Oddi 26 controlssecretions from the liver, pancreas 24, and gallbladder 14 into theduodenum 30 of the small intestine. The opening on the inside of thedescending duodenum 30 after the Sphincter of Oddi 26 is called themajor duodenal papilla 28 (of Vater). Together, the biliary ducts, thegallbladder 14, the cystic duct 16 and the common bile duct 18 comprisethe biliary system (FIG. 1).

The pancreas 24 is a gland organ in the digestive and endocrine systemof vertebrates. It is both an endocrine gland (producing severalimportant hormones, including insulin, glucagon, and somatostatin), aswell as an exocrine gland, secreting pancreatic juice containingdigestive enzymes that pass to the small intestine. These enzymes helpin the further breakdown of the carbohydrates, protein, and fat in thechyme. The pancreatic duct 22, or duct of Wirsung, is a duct joining thepancreas 24 to the common bile duct 18 to supply pancreatic juices whichaid in digestion provided by the exocrine pancreas. The pancreatic duct22 joins the common bile duct 18 just prior to the major duodenalpapilla 28, after which both ducts perforate the medial side of thesecond portion of the duodenum 30 at the major duodenal papilla.

Biliary Disease:

The most common problem that arises in the biliary system is theformation of gallstones, a condition called cholelithiasis.Approximately 20 million Americans have gallstones, and about 1-3% willexhibit symptoms in any given year. In the U.S., gallstones are morecommon among women, with 25% of women having gallstones by the age of 60and 50% by the age of 75, Pregnancy and hormone replacement therapyincrease the risk of forming gallstones. Prevalence is lower forAmerican men: approximately 25% will develop gallstones by the age of75. In the U.S., gallstones are responsible for the highest number ofhospital admissions due to severe abdominal pain.

Gallstones 20, 20′ are most often composed of cholesterol, but may alsobe formed from calcium bilirubinate, in which case they are calledpigment stones. They range in size from a few millimeters to severalcentimeters, and are irregularly shaped solids resembling pebbles. Theycan form in the gallbladder 14, cystic duct 16, and/or the common bileduct 18 (FIG. 2). By themselves, gallstones 20 do not necessarily resultin disease states. This is the case 90% of the time. However, stones cancause infection and inflammation, a condition known as cholecystitis,which is generally the result of restricting or blocking the flow ofbile from the gallbladder 14 and common bile duct 18, or the fluidssecreted by the pancreas 24.

Gallbladder disease may be chronic, and patients who suffer from thismay periodically experience biliary colic. Symptoms include pain in theupper right abdomen near the ribcage, nausea, and/or vomiting. The painmay resolve within an hour of onset, may prove unresponsive toover-the-counter medicines, and may not decrease with changes ofposition or the passage of gas. Recurrence is common, with pain oftenrecurring at the same time of day, but with frequency of less than onceper week. Fatty or large meals may cause recurrence several hours aftereating, often awakening the patient at night. Patients may elect tosuffer from these symptoms for very long periods of time, such as yearsor even decades.

Patients with chronic cholecystitis have gallstones and low-gradeinflammation. Untreated, the gallbladder 14 may become scarred and stiffover time, leading to a condition called dysfunctional gallbladder.Patients who have chronic cholecystitis or dysfunctional gallbladder mayexperience gas, nausea, and abdominal discomfort after meals, andchronic diarrhea.

Acute cholecystitis (a surgical emergency) develops in 1-3% of thosewith symptomatic gallstone disease, and is due to obstruction of thecommon bile duct 18 or cystic duct 16 by stones or sludge. Symptoms aresimilar to biliary colic, though they are more severe and persistent.Pain in the upper right abdomen can be constant and severe, theintensity may increase when drawing breath, and it may last for days.Pain may radiate to the back, under the breastbone or the shoulderblades, and it may be perceived on the left side of the abdomen. Inaddition to nausea and vomiting, one third of patients experience feverand chills. Complications from acute cholecystitis can be serious andlife threatening, and include gangrene, abscesses, perforation of thegallbladder 14 which can lead to bile peritonitis, pus in thegallbladder wall (empyema), fistulae, and gallstone ilius (when agallstone creates a blockage in the small intestine).

When gallstones 20′ become lodged in the common bile duct 18 (FIG. 2),the condition is known as choledocholithiasis. Symptoms for thiscondition include pain, nausea and vomiting, and some patients developjaundice, have dark urine and/or lighter stools, rapid heartbeat, andexperience an abrupt drop in blood pressure. These symptoms can also beaccompanied by fever, chills, and/or severe pain in the upper rightabdomen. Complications from choledocholithiasis can also be veryserious, and include infection of the common bile duct 18 (cholangitis)and inflammation of the pancreas 24 (pancreatitis).

A smaller patient population suffers from gallbladder disease thatoccurs in the absence of gallstones. This condition, called acalculousgallbladder disease, can also be chronic or acute. Chronic acalculousgallbladder disease, also called biliary dyskinesia, is thought to becaused by motility disorders that affect the gallbladder's ability tostore and release bile. Acute acalculous gallbladder disease occurs inpatients who suffer from other serious illnesses which can lead toinflammation of the gallbladder 14 because of a reduction in the supplyof blood to the gallbladder 14 or a reduced ability to contract andempty bile into the duodenum 30.

Cancer can also develop in the gallbladder 14, though this condition israre. Gallstones have been found in 80% of patients with gallbladdercancer. Gallbladder cancer typically develops from polyps, which aregrowths inside the gallbladder 14. When polyps 15 mm across or largerare observed, the gallbladder is removed as a preventive measure. Polypssmaller than 10 mm are widely accepted as posing low risk and are notgenerally removed. When detected early, before the cancer has spreadbeyond the mucosa (inner lining) of the gallbladder, the 5-year survivalrate is approximately 68%. However, gallbladder cancer is not usuallydetected until patients are symptomatic, by which time the disease ismore advanced.

Treatment of Biliary Disease:

The most effective treatment for biliary disease has been surgicalremoval of the gallbladder 14, a procedure called cholecystectomy.Surgical removal of the gallbladder 14 is indicated for patients whoexperience a number of less severe gallstone attacks, cholecystitis,choledocholithiasis, pancreatitis, acalculous biliary pain with evidenceof impaired gallbladder 14 emptying, those at high risk for developinggallbladder cancer, and those who have previously undergone endoscopicsphincterotomy for common bile duct stones. Other treatment modalitiesexist and are frequently used, but gallbladder disease tends to recur inthe majority of patients who forgo cholecystectomy and pursuealternatives. Removal of the gallbladder 14 is highly successful atpermanently eliminating biliary disease. Cholecystectomy is one of themost commonly performed procedures on women. The gallbladder 14 is notan essential organ, and after a period of adjustment post surgery,patients tend to return to more or less normal digestive function.

Cholecystectomy can be performed either as open surgery, which requiresa single larger incision in the upper right abdomen, or laparoscopicsurgery, in which several small instruments are inserted through muchsmaller incisions in the abdomen. Approximately 80% of cholecystectomiesare performed laparoscopically. The primary benefits of this minimallyinvasive approach are faster recovery for the patient, and a reductionin overall healthcare costs. Patients who receive laparoscopiccholecystectomy are usually released the same day. By contrast, patientsreceiving open cholecystectomies typically spend 5-7 days in a hospitalbefore release. 5-10% of laparoscopic procedures convert to openprocedures when difficulties arise, such as injury to major bloodvessels, inadequate access, inadequate visualization, previousendoscopic sphincterotomy, and thickened gallbladder wall. Complicationsfrom cholecystectomy (open or laparoscopic) include bile duct injuries(0.1-0.5% for open, 0.3-2% with a declining trend for laparoscopic),pain, fatigue, nausea, vomiting, and infection. In up to 6% of cases,surgeons fail to identify and remove all gallstones present.

In some cases, the degree of infection and inflammation preventspatients from undergoing immediate cholecystectomy. In these cases, thegallbladder 14 must be treated with antibiotics and anti-inflammatoryagents, and drained through a tube into a reservoir outside the abdomen.Placement of this tube occurs in a procedure called percutaneouscholecystostomy, in which a needle is introduced to the gallbladder 14through the abdomen, fluid is withdrawn, and a drainage catheter isinserted. This catheter drains into an external bag which must beemptied several times a day until the tube is removed. The drainagecatheter may be left in place for up to 8 weeks. In cases where nodrainage catheter is inserted, the procedure is called gallbladderaspiration. Since no indwelling catheter is placed, the complicationrate for gallbladder aspiration is lower than that of percutaneouscholecystostomy.

Treatment methodologies other than cholecystectomy include expectantmanagement, dissolution therapy, endoscopic retrogradecholangiopanctreatograpy (ERCP) with endoscopic sphincterotomy, andextracorporeal shockwave lithotripsy (ESWL).

Expectant management is appropriate for patients who have gallstones butno symptoms, and for non-emergency cases with less severe symptoms. Thisapproach is not recommended when patients are in high risk categories(e.g. high risk for gallbladder cancer) or have very large gallstones(e.g. greater than 3 cm).

Oral dissolution therapy involves the administration of pills containingbile acids that can dissolve gallstones. This approach is onlymoderately effective, and the rate of recurrence of gallstones aftercompletion of treatment is high. It is not appropriate for patients withacute inflammation or stones in the common bile duct (more seriousconditions). Dissolution therapy tends to be more effective for patientswith cholesterol stones, and is sometimes used in conjunction withlithotripsy. Despite its relative ineffectiveness, it is costly:treatment can last up to 2 years and the drugs cost thousands of dollarsper year.

Related to oral dissolution therapy is contact dissolution, a procedurethat involves injection of a solvent such as methyl tert-butyl ether(MTBE) directly into the gallbladder 14. This approach is highlyeffective at dissolving gallstones, but patients may experience severeburning pain.

ERCP (endoscopic retrograde cholangiopancreatograpy) is a procedure inwhich an endoscope is introduced through the mouth of a patient, pastthe stomach to the papilla 28, where the common bile duct 18 emptiesinto the duodenum 30. The overall goal of the procedure is to insertinstruments and tools into the common bile duct 18 via the papilla 28 inorder to treat biliary disease. Typically, endoscopic sphincterotomy isperformed, which is a procedure that enlarges the opening of the papilla28 in the small intestine. This can be accomplished surgically or viaballoon dilation. Contrast agent is introduced into the common bile duct18 to visualize the biliary tree fluoroscopically. Tools for clearingblockages, such as mechanical lithotripsy devices, can be deployed tocrush gallstones and remove the resulting debris. Drainage catheters andstents may also be inserted to facilitate the drainage of bile pastobstructions. Complications from this challenging procedure occur at arate of 5-8%, and include recurrence of stone formation, pancreatitis,infection, bleeding, and perforation.

Extracorporeal shockwave lithotripsy (ESWL) is a technique in whichfocused, high-energy ultrasound is directed at the gallbladder 14. Theultrasound waves travel through the soft body tissue and break up thegallstones. The resulting stone fragments are then usually small enoughto pass through the bile duct into the small intestine. Oral dissolutiontherapy is often used in conjunction with ESWL. This treatment is not incommon use, as less than 15% of the patient population are goodcandidates. However, ESWL is used to treat patients who are notcandidates for surgery. Complications from ESWL include pain in thegallbladder area, pancreatitis, and failure of the gallstone fragmentsto pass into the small intestine.

SUMMARY OF THE INVENTION

Devices for treating biliary disease are disclosed. Suitable devicescomprise, for example, a component configurable for placement within acystic duct of a biliary system of a patient which has a proximal end102 and a distal end 104. In some aspects, a means adaptable forpositioning within a lumen of a cystic duct of a biliary system of apatient is provided which has a proximal end and a distal end. Devicescan further comprise a delivery mechanism for delivering a substance,such as bioresorbable materials or activatable materials. The means forpositioning within a lumen can further provide, for example, a means fordelivering a substance, such as bioresorbable materials or activatablematerials. In some instances, the devices are adaptable and configurableto be removable. Additionally, or alternatively the device are adaptableand configurable to be expandable. Moreover, the devices can beconfigurable such that the device can achieve one or moreconfigurations, such as a deployment configuration, a deliveryconfiguration and a final configuration. In some embodiments, devicescomprise a variable profile, for example, the device can be configurableto be variable along a cross-sectional area of the device. In someaspects, the devices are configurable for deployment by, for example, anendoscope, or by a guidance element such as a guidewire or guidancecatheter. In other aspects a lumen can be provided that is configurableto provide restrictable fluid flow, for example by using one or morefluid control components. Devices can also be configured to comprise avalve. Suitable valves include, for example, a flow-restrictor valve ora one-way valve. Moreover, a means for controlling a material can beprovided, such as a valve, including, for example, a flow-restrictorvalve or a one-way valve. In some configurations of the device it may bedesirable for the device to be flexible.

Still another aspect is directed to a biliary disease treatment devicecomprising: an implant adapted to be delivered by an endoscope, orguidance element such as a guidewire or guidance catheter to agastrointestinal site in proximity to a gallbladder, and further adaptedto form a conduit between the gastrointestinal site and the gallbladder.Devices can further comprise a delivery mechanism for delivering asubstance, such as bioresorbable materials or activatable materials. Insome instances, the devices are adaptable and configurable to beremovable. Additionally, or alternatively the device are adaptable andconfigurable to be expandable. Moreover, the devices can be configurablesuch that the device can achieve one or more configurations, such as adeployment configuration, a delivery configuration and a finalconfiguration. In some embodiments, devices comprise a variable profile,for example, the device can be configurable to be variable along across-sectional area of the device. In some aspects, the devices areconfigurable for deployment by, for example, an endoscope, or by aguidance element such as a guidewire or guidance catheter. In otheraspects the lumen is configurable to provide restrictable fluid flow,for example by using one or more fluid control components. Devices canalso be configured to comprise a valve. Suitable valves include, forexample, a flow-restrictor valve or a one-way valve. In someconfigurations of the device it may be desirable for the device to beflexible.

Yet another aspect is directed to a biliary disease treatment devicecomprising: an implant adaptable to be delivered by percutaneous means,to a gastrointestinal site in proximity to a gallbladder, and furtheradapted to form a conduit means between the gastrointestinal site andthe gallbladder. Percutaneous means includes, for example, guidewire,guiding catheter or endoscope.

Aspects of the invention also include methods of delivering a device totreat biliary disease. The methods of device delivery comprise, forexample, using an endoscope to place guidance element, such as aguidewire or guidance catheter, between an access lumen and agallbladder; inserting a delivery catheter over the guidance element andinto the gallbladder; delivering a cystic duct defunctionalizing deviceon the guidance element; and positioning the cystic ductdefunctionalizing device within a cystic duct. Additional method stepscan include the step of passively retaining a distal end of theguidewire in the gallbladder while the guidewire is used to deliveradditional elements. Moreover, the method can include the step ofretaining a distal end of the guidewire within the gallbladder,retaining a distal end of the guidewire within the cystic duct, and/orretaining a distal end of the guidewire within the common bile duct.Additionally, gallstones can be removed through the created lumen, ifdesired. Additionally, in some instances, the method can include thestep of localizing the gallbladder via endoscopic ultrasound and/oraltering or altering and removing gallstones. It will be appreciated bythose skilled in the art, that in some instances, it may be desirable toclear obstructions within the gallbladder. Moreover, it will beappreciated that the methods involved herein facilitated treatment ofbiliary disease without removal of the gallbladder. In still othermethods, it may be desirable to also visualize a treatment area, before,during, or after any of the other method steps. In still other methods,a biological duct can be formed in situ from a patient's tissue.Moreover, the cystic duct defunctionalizing device can be changed, ifdesired, from a delivery configuration to a deployment configuration,from a delivery configuration to a final configuration, and/or from adeployment configuration to a final configuration. In still otheraspects of the method, a cross-sectional profile of the cystic ductdefunctionalizing device can be reduced. In other aspects, a valve canbe operated to restrict fluid flow. In some instances it may bedesirable to defunctionalize the cystic duct in situ. Suchdefunctionalizing can be achieved by, for example, delivering asubstance into a space within the cystic duct. As will be appreciated bythose skilled in the art, a wide range of substances can be delivered,including, for example, gels, foams, sclerosing agents, adhesives,bioadhesives, anti-inflammatory and inflammatory agents. Moreover, somesubstances can be selected that are capable of activation in situ. Theamount of substance delivered can vary, as desired, and can includedelivering an amount sufficient to fill, or substantially fill, thelumen of the cystic duct, or in the case of an activatable substance, anamount sufficient to result in an activated substance amount sufficientto fill, or substantially fill, the lumen of the cystic duct. In otheraspects of the method, the step of defunctionalizing the cystic duct isachievable by delivering a plug or device into a space, or lumen, withinthe cystic duct. Suitable plugs may be configurable either internally orexternally to seat within the lumen of the cystic duct. Moreover plugsor devices can further comprise one or more thread profiles, ridges orsteps about its exterior surface adapted to aid in seating the devicewithin the lumen of the duct. The plugs or devices can further comprisea valve.

Another aspect of the invention is directed to a kit for treatingbiliary disease. Kits include, for example, one or more devicesconfigurable to be positioned within a cystic duct; and optionally acompound for delivery to a tissue. Other components of the kit include,one or more of, a catheter, a guidewire, an ablation device, asclerosing agent, antibiotic agents, inflammatory agents,anti-inflammatory agents, biocompatible gels, biocompatible foams,activatable materials, scissors, scalpels, swabs, syringes, hemostats,lubricants, needles, snares, antiseptics, and anesthetics.

Still another aspect of the invention is directed to a method oftreating biliary disease comprising: accessing a lumen associated with agallbladder; defunctionalizing a cystic duct. An aspect of the methodenables the gallbladder to be left in situ. Additionally, the step ofdefunctionalizing the cystic duct can further comprise the step ofdelivering a substance to at least one of the cystic duct or thegallbladder. An amount of substance can be delivered such that itoccupies, or substantially occupies the lumen, or is activated to occupyor substantially occupy the lumen of the cystic duct. One or moresuitable substances can be delivered including, for example,antibiotics, inflammatory agents, and anti-inflammatory agents. In someinstances, the method includes the step of preventing bile from enteringthe gallbladder lumen. Additionally, the method can include the step oflocalizing the gallbladder via endoscopic ultrasound. In other aspectsof the method, the step of accessing the gallbladder is achieved via thegastrointestinal tract, such as by accessing the gastrointestinal tractat a duodenum. Additional aspects of the method include, for example,one or more of sclerosing, necrotizing or ablating tissue. Ablationtechniques can, for example, be selected from the group comprisingcryoablation, thermal ablation, chemical ablation, radio frequencyablation, ultrasound ablation, and microwave ablation. In someinstances, a fluid can be delivered wherein the fluid is delivered, forexample, with an angular orientation, moreover fluid can be deliveredwith at least one of a 360 degree radial pattern, a sharp stream, and acone shape. Still further, the fluid can be delivered with a devicecomprising an articulating member or a means for articulating. In someaspects of the method it may be desirable to apply a vacuum to a lumenof the cystic duct or the gallbladder, and/or apply an adhesive to thelumen of the cystic duct. Additionally, in some instances the step ofdefunctionalizing the cystic duct may further comprise physicallyblocking a lumen of the cystic duct, such as with a plug, device, meansfor blocking or means for plugging.

Yet another aspect of the invention is directed to a device for treatingbiliary disease comprising a plug, device, means for blocking or meansfor plugging, adaptable and configurable to be positioned within acystic duct of a patient having a proximal end and a distal end and isconfigurable either internally or externally to seat within a lumen ofthe cystic duct after deployment. The external configuration of theplug, device, or plugging means can be configurable to have one or moreof threads, ridges, steps, or means for securing. Moreover, the ridges,steps or means for securing can be fixed or activatable. Additionally,the plug, device or plugging means can further comprise a valve, such asa one-way valve, or means for controlling or restricting a flow of fluidor flowable material. In some aspects the plug, device or plugging meanscan be positioned within or proximal to the cystic duct.

Another aspect of the invention is directed to the use of any of thedevices disclosed herein for use in the treatment of biliary disease.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention will be set forth with particularityin any claims presented based on this application. A betterunderstanding of the features and advantages of the present inventionwill be obtained by reference to the following detailed description thatsets forth illustrative embodiments, in which the principles of theinvention are utilized, and the accompanying drawings of which:

FIG. 1 illustrates an overview of the biliary system;

FIG. 2 illustrates the biliary system with gallstones;

FIG. 3 illustrates an endoscope accessing the biliary system via theintestinal system;

FIGS. 4A-E illustrate cystic duct defunctionalization devices;

FIG. 5 illustrates a cystic duct defunctionalization device incombination with a guidewire; and

FIG. 6 illustrates a cystic duct plug with 1-way valve.

DETAILED DESCRIPTION OF THE INVENTION

Devices, systems, methods and kits provided herewith can obviate theneed for a plurality of procedures, including, for example: 1)percutaneous cholecystostomy, 2) cholecystectomy, 3) percutaneoustrans-hepatic cholangiography (PTHC), and 4) endoscopic retrogradecholangiopancreatography (ERCP). Additionally, disclosed treatmentmodalities enable treatment of a distal common bile duct 18 obstruction,e.g. secondary to pancreatic carcinoma, cholagiocarcinoma, and/orampullary carcinoma. As will be appreciated by those skilled in the art,the conventional standard of care for treating biliary disease has beensurgical removal of the gallbladder 14 and closure of the cystic duct16. While this has proven to be an effective mechanism for permanentlyeliminating biliary disease and its recurrence, the present inventionseeks to accomplish the same end in a less invasive and less costly way.This may be achieved by treating biliary disease without requiring theremoval of the gallbladder 14. Methods and apparatus are described inthis application that are intended to effectively treat biliary diseasewith the gallbladder 14 and cystic duct 16 left in situ bydefunctionalizing the cystic duct.

Defunctionalization of the Cystic Duct:

In order to treat gallbladder 14 disease while leaving the gallbladder14 in situ, it may be desirable to defunctionalize the cystic duct 16.The cystic duct 16 connects the gallbladder 14 and the common bile duct18 (see FIG. 1), and is the flow path for bile into and out of thegallbladder 14. An objective of defunctionalizing the cystic duct 16 isto prevent bile from reaching the gallbladder 14. The gallbladder 14 maybe otherwise unaltered, or it may be altered—e.g. a conduit or shunt maybe placed for access and/or drainage, the gallbladder 14 may bedefunctionalized, etc. When bile is unable to enter the cystic duct 16,and therefore the gallbladder 14, the gallbladder 14 will also beeffectively defunctionalized, whether or not any other treatment isperformed. Gallstones may form anywhere that bile is present in thebiliary system, so preventing bile from flowing in the cystic duct 16may prevent the formation of gallstones in the cystic duct 16 andgallbladder 14. Defunctionalization of the cystic duct 16 may be long-or short-term, temporary or permanent. The entire length of the cysticduct 16 may be defunctionalized, or it may be performed at one or morediscrete locations. The treatment may be applied anywhere along thelength of the cystic duct 16, from the point where it joins the commonbile duct 18 to the point where it interfaces with the gallbladder 14.However, the preferred treatment location for defunctionalizing thecystic duct 16 is as close to the junction with the common bile duct 18as possible without substantially affecting the function of the commonbile duct 18.

In holding with the other methods and apparatus described in thisapplication, it is most desirable to effect defunctionalization of thecystic duct 16 from within the gallbladder 14, inside the cystic duct16, and/or inside the common bile duct 18. This eliminates the need forexternal, surgical access to these anatomical structures. Optionally,defunctionalization of the cystic duct 16 is achieved by the use ofimplements delivered endoscopically or means for accessing the cysticduct percutaneously. In some instances, directly visualizing the devicesand navigational devices used may also be desirable, and may facilitatecontrol and treatment. Visualization may be achieved by any suitablemechanism known in the art, including, for example, endoscopicultrasound (EUS), or by using a small daughter endoscope (e.g. acystoscope), or by using catheters incorporating small imaging sensorsat the distal end (e.g. Avantis' Third Eye) and fiber optic imagingbundles (e.g. Boston Scientific's SpyGlass). Visualization and guidancemay also be achieved via external imaging methods, such as fluoroscopy(with or without the use of contrast agent), ultrasound, X-ray, etc.

Defunctionalization of the cystic duct 16 may be accomplished by avariety of mechanisms, including, but not limited to, ablation methods(e.g. cryo-, thermal-, RF, microwave, ultrasound, etc.) and mechanicalmethods (e.g. plugs, stoppers, sutures, staples, clamps, clips,adhesives, bioadhesives, vacuum with adhesives/bioadhesives, vacuumwithout adhesives/bioadhesives, etc.). Regardless of the method used, itmay be helpful to begin the process by inserting a guidance element 530,such as a guidewire, guidance catheter or any suitable means foraccessing the cystic duct 16 from within the gallbladder 14, though aconduit that connects the gallbladder 14 lumen to the access lumen, e.g.at or near the duodenum 30, or from within the common bile duct 18, asmay be done during ERCP. A guidance element 530 (FIG. 5) (e.g. aguidewire, guidance catheter, etc.) may be useful for inserting andnavigating items into the cystic duct 16, such as ablation catheters,visualization catheters, mechanisms of treating gallstones within thecystic duct 16, devices 520 for defunctionalizing the cystic duct 16,and other mechanisms of defunctionalizing the cystic duct 16. Since thecystic duct 16 is funnel-shaped (with a larger diameter at the openinginto the gallbladder 14 than at the junction with the common bile duct18), and spirals as it progresses (an anatomical feature called thevalves of Heister), it may be easily traversed with a guidance element530, such as a guidewire or guidance catheter, from within thegallbladder 14 simply by pushing. However, the guidance element 530 maybe configured or configurable to facilitate advancement. Moreover,alternate shapes of the guidance element 530 may facilitate advancement,such as a cork-screw shape, spiral shape, or a tip that ispreferentially bent to one side. In these cases, successfully advancingthe guidance element 530 into the cystic duct 16 may be achieved bypushing, torquing (rotating), or a combination of pushing and torquing.

If defunctionalization is achieved by physically blocking the cysticduct 16, a cystic duct defunctionalization device 420 serving a similarfunction as, for example, a bottle stopper may be used (FIG. 4A). Thedefunctionalization device 420 has a proximal end and a distal end. Sucha device 420 may be inserted into the cystic duct 16 from thegallbladder 14, through a conduit that connects the gallbladder 14 to anaccess lumen such as the duodenum 30. The plug 420 may be insertedbefore, during, or after other treatments for inflammation, infection,gallstones, etc. have been administered or completed. The plug 420 maybe left in place for a limited period of time, or permanently. The plug420 or means for plugging the cystic duct may be comprised of anysuitable biocompatible material, such as silicone,polytetrafluroethylene (PTFE), stainless steel, titanium, shape memorymaterials (e.g. Nitinol), etc. The device 420 may be configured orconfigurable to provide a means for blocking the cystic duct.

Devices 420 may optionally incorporate features that aid in retainingand securing the device in place. Such features may be inactive (thatis, fixed and integral to or incorporated into the devices), e.g. aspiral thread pattern 422 (in which case, the devices should be rotatedinto position in the cystic duct 16 at installation, FIG. 4B), one ormore ridges 423 (FIG. 4 c), and/or one or more backward-facing steps 424resembling a hose barb (FIG. 4D). Each of these one or more threads 422,ridges 423, and steps 424 features enable the device 420 to be securedwithin the cystic duct 14. Alternately, the retaining features may beactive 425 so that they may be activated once the device is in thedesired position, e.g. with shape memory alloys (e.g. Nitinol) or withmechanically triggered movable elements (FIG. 4E).

Additionally, a plug or stopper device 620 may have one or more flowcontrol elements, such as 1-way valves 640 which allow flow out of thegallbladder 14 and cystic duct 16, but does not allow flow into thecystic duct 16 or gallbladder 14 (FIG. 6). This may be useful in caseswhere drainage of the gallbladder 14 and/or cystic duct 16 is desired,and provides either a primary or secondary flow path for fluids.Additionally, activatable materials can be delivered to the cystic duct.Suitable activatable materials include, for example, sclerosingsubstances, gels, foams, adhesives, bioadhesives. Any of suchactivatable materials may be selected so that they are absorbed or breakdown within the body over a desired period of time. Additionally, avacuum may be applied to the cystic duct in order to close orsubstantially close it. This may be done in combination with the use ofany of the other techniques described herein.

Since stones 20 may be present in the cystic duct 16 at the time oftreatment, it may be necessary to eliminate them before, during, orafter defunctionalization. This may be achieved using mechanicallithotripsy, snares, chemical/contact dissolution with substances suchas methyl tertiary-butyl ether (MTBE), ultrasound energy, or any otheruseful or effective mechanism of breaking up and/or removing gallstones.Removal of gallstones through a conduit placed in the gallbladder 14allows clinicians to access the cystic duct 16 from the reversedirection, which is not possible with conventional techniques. This maydramatically facilitate the process of treating gallstones 20 in thecystic duct 16 and common bile duct 18, which can be difficult usingconventional techniques.

A method of treating biliary disease involves using an endoscope 310 toaccess a region in the gastrointestinal (GI) tract to which the cysticduct 16 is in close proximity, locating the cystic duct 16, accessingthe cystic duct 16, and then treating the underlying condition that ledto the need for intervention (FIG. 3). Treatments may also include, butare not limited to: providing for drainage of the gallbladder 14 and/orthe biliary tree, delivering antibiotics, inflammatory,anti-inflammatory agents (any of which may be short-term acting, fastacting, or time release), and/or other substances (e.g. adhesives,bioadhesives, etc.) and/or activatable materials to the gallbladder 14and/or biliary tree, removing gallstones 20, facilitating thedestruction and subsequent removal of gallstones, clearing obstructions,delivering catheters, delivering stents (drug coated or not drugcoated), temporarily or permanently defunctionalizing the cystic duct16, temporarily or permanently defunctionalizing the gallbladder 14.Devices and therapies can be delivered in a single treatment, withminimal likelihood of or necessity for follow-up or repeat procedures.

Localization of the gallbladder 14 can be performed via endoscopicultrasound (EUS) by accessing the wall of the GI tract with an endoscope310 as shown in FIG. 3. Localization may also be achieved by any othermethod that visualizes anatomical features, such as fluoroscopy, x-rays,magnetic resonance imaging (MRI), computed axial tomography (CT) scans,ultrasound imaging from outside the body, or any method of anatomicalimaging and visualization.

Once the gallbladder 14 has been located, it may be accessed and/ortreated through the wall of the GI tract 350 (or any lumen in proximityto the gallbladder 14) with tools and devices (e.g. needles, guidewires,guidance catheters, shunts, dilators, etc.) delivered through, forexample, an endoscope 310. Such tools and devices may be inserted downthe length of the endoscope's working channel 312, or loaded onto ornear the distal end of the endoscope 310. Alternately, tools and otherdevices may be used that do not require the aid of the endoscope fornavigation or delivery. Direct visualization may be provided by theendoscope 310 during the procedure, as well as irrigation, suction, andinsufflation.

Though the preferred location for accessing the gallbladder lumen is theduodenum 30, it may also be readily achieved through the wall of otherregions of the GI tract, such as the stomach or the jejunum, forexample. Thus, any lumen in close proximity to the gallbladder 14 is acandidate for access to and treatment of the gallbladder 14 and othermembers of the biliary system.

The devices and methods disclosed herein facilitate defunctionalizingthe cystic duct without the need for surgery.

Kits:

All of the devices required to deliver and install a conduit, treatand/or defunctionalize the cystic duct 16, may be packaged in a kit.Bundling all devices, tools, components, materials, and accessoriesneeded to perform these procedures into a kit may enhance the usabilityand convenience of the devices, and also improve the safety of theprocedure by encouraging clinicians to use the items believed to resultin the best outcomes. The kit may be single-use or reusable, or it mayincorporate some disposable single-use elements and some reusableelements. The kit may contain, but is not limited to, the following:implantable and/or non-implantable devices; delivery devices (e.g.,needles, guidewires, guidance catheters, dilators, etc.); ballooninflation/deflation accessories; syringes; fluid flow, temperature, andpressure measurement instruments; scissors; scalpels; clips; ablationcatheters; endoscopic tools (e.g. lithotripsy devices, snares, graspers,clamps, forceps, etc.). The kit may be supplied in a tray, whichorganizes and retains all items so that they can be quickly identifiedand used.

DESCRIPTION OF OTHER USES

The techniques and devices described in this application may provebeneficial in applications beyond their initial use in the treatment ofbiliary disease.

For example, they may prove to be an effective mechanism of treatingcholangitis (infection of the common bile duct 18). This condition isusually bacterial, and occurs when the bile duct is blocked bygallstones 20′ or a tumor. Traditional treatment involves the insertionof a stent or drainage catheter into the common bile duct 18 to allowbile to drain into the duodenum 30 from locations above the obstruction.Placement of a conduit into the gallbladder 14 may allow for analternate method of draining bile and/or other fluids into the duodenum30. Any blockage in the common bile duct 18 between the entrance of thecystic duct 16 and the duodenum 30 may be treated in this way. See FIG.2.

Another use of the devices and techniques described elsewhere in thisapplication may be to create anastomoses between any body lumens inproximity to one another. This may include, but is not limited to: smallbowel to small bowel anastomoses, small bowel to large bowelanastomoses, large bowel to large bowel anastomoses, and stomach tosmall bowel anastomoses. Additionally, creating a conduit between thestomach and other body lumens may be useful and effective for treatingand/or managing obesity.

Another use of the devices and techniques described herein is fordrainage of any body lumen into another body lumen in proximity, forexample, the drainage of pancreatic pseudocysts.

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the invention describedherein may be employed in practicing the invention. It is intended thatthe following claims define the scope of the invention and that methodsand structures within the scope of these claims and their equivalents becovered thereby.

1. A device for treating biliary disease comprising: a componentconfigurable for placement within a cystic duct of a biliary system of apatient which has a proximal end and a distal end.
 2. The device ofclaim 1 further comprising a delivery mechanism for delivering asubstance.
 3. The device of claim 1 wherein the device is formed from atleast one of a bioresorbable material or an activatable material.
 4. Thedevice of claim 1 wherein the device is removable.
 5. The device ofclaim 1 wherein the device is expandable.
 6. The device of claim 1further comprising one or more configurations selected from a deploymentconfiguration, a delivery configuration and a final configuration. 7.The device of claim 6 further comprising a variable profile.
 8. Thedevice of claim 1 wherein a cross-sectional area of the device isvariable along a length.
 9. The device of claim 1 wherein the device isconfigurable for deployment by an endoscope.
 10. The device of claim 1wherein the device is configurable for deployment by a guidance element.11. The device of claim 1 wherein a lumen is provided that isconfigurable to provide restrictable fluid flow.
 12. The device of claim10 further comprising one or more fluid control components. 13.(canceled)
 14. (canceled)
 15. The device of claim 1 wherein the deviceis flexible.
 16. A biliary disease treatment device comprising: animplant adapted to be delivered by an endoscope, guidance element to agastrointestinal site in proximity to a gallbladder, and further adaptedto form a conduit between the gastrointestinal site and the gallbladder.17. (canceled)
 18. (canceled)
 19. (canceled)
 20. (canceled) 21.(canceled)
 22. (canceled)
 23. (canceled)
 24. (canceled)
 25. (canceled)26. (canceled)
 27. (canceled)
 28. A method of delivering a device totreat biliary disease comprising: a. using an endoscope to place aguidance element between an access lumen and a gallbladder; b. insertinga delivery catheter over the guidance element and into the gallbladder;c. delivering a cystic duct defunctionalizing device on the guidanceelement; and d. positioning the cystic duct defunctionalizing devicewithin a cystic duct.
 29. (canceled)
 30. (canceled)
 31. (canceled) 32.(canceled)
 33. (canceled)
 34. The method of claim 28 further comprisingthe step of localizing the gallbladder via endoscopic ultrasound. 35.The method of claim 28 further comprising the step of removinggallstones.
 36. The method of claim 28 further comprising the step ofaltering gallstones.
 37. The method of claim 36 further comprising thestep of removing the altered gallstones.
 38. (canceled)
 39. The methodof claim 28 wherein the biliary disease is treated without removal ofthe gallbladder.
 40. The method of claim 28 wherein the biliary diseaseis treated without removal of the cystic duct.
 41. (canceled)
 42. Themethod of claim 28 further comprising the step of forming a biologicalduct in situ from a patient's tissue.
 43. The method of claim 28 furthercomprising the step of changing the cystic duct defunctionalizing devicefrom a delivery configuration to a deployment configuration.
 44. Themethod of claim 28 further comprising the step of changing the cysticduct defunctionalizing device from a delivery configuration to a finalconfiguration.
 45. The method of claim 28 further comprising the step ofchanging the cystic duct defunctionalizing device from a deploymentconfiguration to a final configuration.
 46. The method of claim 28further comprising the step of reducing a cross-sectional profile of thecystic duct defunctionalizing device.
 47. (canceled)
 48. The method ofclaim 28 further comprising the step of defunctionalizing the cysticduct in situ.
 49. The method of claim 48 wherein the step ofdefunctionalizing is achieved by delivering a substance into a spacewithin the cystic duct.
 50. The method of claim 49 wherein the deliveredsubstance is selected from the group consisting of gel and foam.
 51. Themethod of claim 49 further comprising the step of activating thedelivered substance in situ.
 52. The method of claim 49 furthercomprising delivering an amount of substance sufficient to fill, orsubstantially fill, the cystic duct lumen.
 53. The method of claim 48wherein the step of defunctionalizing is achieved by delivering a pluginto a space within the cystic duct.
 54. The method of claim 53 whereinthe plug is configurable either internally or externally to seat withinthe lumen.
 55. The method of claim 53 wherein the plug further comprisesone or more thread profiles, ridges or steps about its exterior surface.56. (canceled)
 57. A kit for treating biliary disease comprising: a. adevice configurable to be positioned within a cystic duct; andoptionally b. a compound for delivery to a tissue.
 58. (canceled) 59.(canceled)
 60. (canceled)
 61. (canceled)
 62. (canceled)
 63. (canceled)64. (canceled)
 65. (canceled)
 66. A method of treating biliary diseasecomprising: a. accessing a lumen associated with a gallbladder; b.defunctionalizing a cystic duct.
 67. (canceled)
 68. (canceled) 69.(canceled)
 70. The method of claim 69 wherein the substance is one ormore of antibiotics, inflammatory agents, and anti-inflammatory agents.71. The method of claim 66 further comprising the step of preventingbile from entering the gallbladder lumen.
 72. (canceled)
 73. The methodof claim 66 further comprising the step of accessing the gallbladder viathe gastrointestinal tract.
 74. The method of claim 73 wherein the stepof accessing is performed in the gastrointestinal tract at a duodenum.75. The method of claim 73 wherein the step of defunctionalizing thecystic duct further comprises one or more of sclerosing, necrotizing orablating tissue.
 76. The method of claim 75 wherein an ablationtechnique is selected from the group comprising cryoablation, thermalablation, chemical ablation, radio frequency ablation, ultrasoundablation, and microwave ablation.
 77. The method of claim 73 furthercomprising the step of delivering a fluid with an angular orientation.78. The method of claim 73 further comprising the step of delivering afluid with at least one of a 360 degree radial pattern, a sharp stream,and a cone shape.
 79. The method of claim 73 further comprising the stepof delivering a fluid with a device comprising an articulating member.80. The method of claim 73 wherein the step of defunctionalizing thecystic duct further comprises applying a vacuum to a lumen of the cysticduct or the gallbladder.
 81. The method of claim 80 further comprisingthe step of applying all adhesive to the lumen of the cystic duct. 82.(canceled)
 83. A device for treating biliary disease comprising a plugadapted and configurable to be positioned within a lumen of a cysticduct of a patient having a proximal end and a distal end and isconfigurable either internally or externally to seat within the lumenafter deployment.
 84. The device of claim 83 wherein the externalconfiguration is one or more of threads, ridges and steps. 85.(canceled)
 86. (canceled)
 87. The device of claim 83 wherein the plug ispositioned within or proximal to a cystic duct.